Abstract

Introduction

Survivors of critical illness often have significant long-term brain dysfunction,
and routine clinical procedures like mechanical ventilation (MV) may affect long-term
brain outcome. We aimed to investigate the effect of the increase of tidal volume
(Vt) on brain activation in a rat model.

Methods

Male Sprague Dawley rats were randomized to three groups: 1) Basal: anesthetized unventilated
animals, 2) low Vt (LVt): MV for three hours with Vt 8 ml/kg and zero positive end-expiratory
pressure (ZEEP), and 3) high Vt (HVt) MV for three hours with Vt 30 ml/kg and ZEEP.
We measured lung mechanics, mean arterial pressure (MAP), arterial blood gases, and
plasma and lung levels of cytokines. We used immunohistochemistry to examine c-fos
as a marker of neuronal activation. An additional group of spontaneously breathing
rats was added to discriminate the effect of surgical procedure and anesthesia in
the brain.

Results

After three hours on LVt, PaO2 decreased and PaCO2 increased significantly. MAP and compliance remained stable in MV groups. Systemic
and pulmonary inflammation was higher in MV rats than in unventilated rats. Plasma
TNFα was significantly higher in HVt than in LVt. Immunopositive cells to c-fos in
the retrosplenial cortex and thalamus increased significantly in HVt rats but not
in LVt or unventilated rats.

Conclusions

MV promoted brain activation. The intensity of the response was higher in HVt animals,
suggesting an iatrogenic effect of MV on the brain. These findings suggest that this
novel cross-talking mechanism between the lung and the brain should be explored in
patients undergoing MV.